• Skip to primary navigation
  • Skip to main content
  • Skip to primary sidebar
MRC Laboratory of Molecular Biology

MRC Laboratory of Molecular Biology

One of the world's leading research institutes, our scientists are working to advance understanding of biological processes at the molecular level - providing the knowledge needed to solve key problems in human health.

  • Home
  • About LMB
  • Research
  • Research Groups
  • Students
  • Recruitment
  • Life at the LMB
  • Achievements
  • News & Events
Home > Insight on Research > New hypothesis for the formation of macropinocytic cups

New hypothesis for the formation of macropinocytic cups

Published on 14 December, 2016

Dictyostelium cell making four macropinosomes, each of which is organised around a patch of PIP3 (orange) with SCAR/WAVE recruited to its perimeter (green)

Macropinocytosis, the cellular uptake of fluids from the environment, is employed by a variety of cells and requires the formation of a cup-shaped structure that protrudes from the cell’s surface and captures gulps of medium. Polymerisation of actin under the plasma membrane drives the extension of macropinocytic cups. However, until now it has been unclear how the actin forming the walls of the cup is shaped into a ring. Work by Douwe Veltman from Rob Kay’s group, in the LMB’s Cell Biology Division, in collaboration with Eric Betzig and Bi-Chang Chen at the Janelia Research Campus in the USA and Robert Insall at the Beatson Institute in Glasgow, has resulted in the formation of a new hypothesis for how these cups form.

Using lattice light sheet microscopy, which generates 3D images, and other advanced microscopy, in combination with fluorescent reporters and mutants, they have shown that during cup formation, a patch of active Ras and PIP3 is generated in the plasma membrane around which the SCAR/WAVE complex is recruited in a ring, avoiding the patch centre. It is SCAR/WAVE that then leads to actin polymerisation to drive extension of the cup walls.

This hypothesis, if true, is widely significant as many cell types form these specialised feeding macropinocytic cup structures. Cancer cells use macropinocytosis to feed on nutrient-rich fluids in the body and immune cells employ the process to sample antigens from their environment. In addition, macropinocytosis is also exploited by bacteria and viruses to gain entry to a host cell, and it may be a mechanism by which neurodegenerative diseases spread in the brain. As a result, macropinocytosis is a potential target for new drugs to treat a range of diseases and an improved understanding of the underlying process will aid in drug development.

Video Player
https://www2.mrc-lmb.cam.ac.uk/wordpress/wp-content/uploads/2.-AX2_Macropinocytosis_Bessel_RacActin_1.mp4
00:00
00:00
00:00
Use Up/Down Arrow keys to increase or decrease volume.

Top view of a Dictyostelium cell making macropinosomes as viewed with a lattice sheet microscope.  The cell makes two modified proteins which reveal the location of its F-actin cytoskeleton (purple) and of an active Rac protein that controls formation of this cytoskeleton (green).  Both are recruited to the macropinocytic cups.

This work was funded by the MRC and the BBSRC.

Further references:

Paper in eLife
Rob’s group page
Robert Insall’s group page
Eric Betzig’s group page

Primary Sidebar

Search

  • Privacy & Cookies
  • Contact Directory
  • Freedom of Information
  • Site Map
Find Us
©2025 MRC Laboratory of Molecular Biology,
Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. 01223 267000

The MRC is part of UK Research and Innovation

Contact Us

This site uses cookies. The LMB may use cookies to analyse how you use our website. We use external analysis systems which may set additional cookies to perform their analysis. These cookies (and any others in use) are detailed in our Privacy and Cookies Policy and are integral to our website. You can delete or disable these cookies in your web browser if you wish, but then our site may not work as it is designed. Ok